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Jay S Naik, Jessica M Osmond, Benjimen R Walker, Nancy L Kanagy
Hydrogen sulfide (H2S) is a recently described gaseous vasodilator produced within the vasculature by the enzymes cystathionine γ-lyase and 3-mercaptopyruvate sulfurtansferase. Previous data demonstrate that endothelial cells (EC) are the source of endogenous H2S production and are required for H2S-induced dilation. However, the signal transduction pathway activated by H2S within EC has not been elucidated. TRPV4 and large conductance Ca(2+)-activated K channels (BK channels) are expressed in EC. H2S-induced dilation is inhibited by luminal administration of iberiotoxin and disruption of the endothelium...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
Lovish Marwaha, Yashika Bansal, Raghunath Singh, Priyanka Saroj, Ranjana Bhandari, Anurag Kuhad
Neuropathic pain is a debilitating disease which affects central as well as peripheral nervous system. Transient receptor potential (TRP) channels are ligand-gated ion channels that detect physical and chemical stimuli and promote painful sensations via nociceptor activation. TRP channels have physiological role in the mechanisms controlling several physiological responses like temperature and mechanical sensations, response to painful stimuli, taste, and pheromones. TRP channel family involves six different TRPs (TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPA1) which are expressed in pain sensing neurons and primary afferent nociceptors...
October 18, 2016: Inflammopharmacology
Jason Fleming, Dianna Quan
We present a patient with congenital spinal muscular atrophy associated with pain, subjective sensory loss, right talipes equinovarus, delayed walking, and progressive gait impairment. A sister and niece reportedly had Charcot-Marie-Tooth 1A, but the patient's electromyogram showed an axonal motor neuropathy or neuronopathy. We identified a c.806G>A TRPV4 gene mutation causing an Arg269His amino acid substitution. TRPV4 mutations cause variable phenotypes including axonal sensorimotor neuropathy and motor neuropathy or neuronopathy...
September 16, 2016: Neuromuscular Disorders: NMD
Nan Zhang, Shengchang Yang, Chang Wang, Jianghua Zhang, Lifang Huo, Yiru Cheng, Chuan Wang, Zhanfeng Jia, Leiming Ren, Lin Kang, Wei Zhang
Alzheimer's disease (AD) and type II diabetes mellitus (DM2) are the most common aging-related diseases and are characterized by β-amyloid and amylin accumulation, respectively. Multiple studies have indicated a strong correlation between these two diseases. Amylin oligomerization in the brain appears to be a novel risk factor for developing AD. Although amylin aggregation has been demonstrated to induce cytotoxicity in neurons through altering Ca(2+) homeostasis, the underlying mechanisms have not been fully explored...
October 12, 2016: Neuropharmacology
Takashi Nishida, Satoshi Kubota, Eriko Aoyama, Nobuyasu Yamanaka, Karen M Lyons, Masaharu Takigawa
OBJECTIVE: CCN family protein 2/connective tissue growth factor (CCN2/CTGF) promotes cartilage regeneration in experimental osteoarthritis (OA) models. However, CCN2 production is very low in articular cartilage. The aim of this study was to investigate whether or not CCN2 was promoted by cultured chondrocytes treated with low-intensity pulsed ultrasound (LIPUS) and to clarify its mechanism. METHODS: Human chondrocytic cell line HCS-2/8, rat primary epiphyseal and articular cartilage cells, and Ccn2-deficient chondrocytes that impaired chondrocyte differentiation, were treated with LIPUS for 20 min at 3...
October 8, 2016: Osteoarthritis and Cartilage
Chao Xue, Jun Gong, Yuming Guo, Jun Yin, Xiaohua He, Hua Huang, Xuefeng Zhou, Jinping Zhao
BACKGROUND: TRPV4, a non-selective cation channel, is involved in lipometabolism and atherosclerosis. However, whether TRPV4 participates in oxygenized low density lipoprotein (oxLDL)-induced foam cell formation remains unknown. The present study investigates the effect of oxLDL on the expression of TRPV4 in macrophages and its underlying mechanisms. METHODS: The expression of TRPV4 in RAW264.7 and phorbol-12-myristate-13-acetate (PMA) induced U937, THP-1 cells was detected by immunofluorescence, and western blot was used to detect the TRPV4 expression before and after PMA induction...
October 5, 2016: Minerva Medica
Takefumi Kamakura, Makoto Kondo, Yoshihisa Koyama, Yukiko Hanada, Yusuke Ishida, Yukiko Nakamura, Takahiro Yamada, Yasumitsu Takimoto, Tadashi Kitahara, Yoshiyuki Ozono, Arata Horii, Takao Imai, Hidenori Inohara, Shoichi Shimada
Transient receptor potential vanilloid (TRPV) 4 is a nonselective cation channel expressed in sensory neurons such as those in the dorsal root and trigeminal ganglia, kidney, and inner ear. TRPV4 is activated by mechanical stress, heat, low osmotic pressure, low pH, and phorbol derivatives such as 4α-phorbol 12,13-didecanoate (4α-PDD). We investigated the expression of TRPV4 in rat vestibular ganglion (VG) neurons. The TRPV4 gene was successfully amplified from VG neuron mRNA using reverse-transcription polymerase chain reaction...
October 6, 2016: Audiology & Neuro-otology
Wei-Chia Lee, You-Lin Tain, Kay L H Wu, Steve Leu, Julie Y H Chan
Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE...
October 5, 2016: Scientific Reports
Patrick Kanju, Wolfgang Liedtke
TRPV4 ion channels are osmo-mechano-TRP channels with pleiotropic function and expression in many different types of tissues and cells. They have also been found involved in pain and inflammation. Studies have focused on the role of TRPV4 in peripheral sensory neurons, but its expression and function in central nervous glial cells and neurons has also been documented. In this overview, based on the senior author's lecture at the recent physiology meeting in Dublin, we concisely review evidence of TRPV4 expression and function in the CNS, and how TRPV4 function can be modulated for therapeutic benefit of neuro-psychiatric disorders...
October 4, 2016: Experimental Physiology
Jinfeng Teng, Stephen H Loukin, Andriy Anishkin, Ching Kung
We have some generalized physical understanding of how ion channels interact with surrounding lipids but few detailed descriptions on how interactions of particular amino acids with contacting lipids may regulate gating. Here we discovered a structure-specific interaction between an amino acid and inner-leaflet lipid that governs the gating transformations of TRPV4 (transient receptor potential vanilloid type 4). Many cation channels use a S4-S5 linker to transmit stimuli to the gate. At the start of TRPV4's linker helix is leucine 596...
October 3, 2016: Proceedings of the National Academy of Sciences of the United States of America
Dragana Srebro, Sonja Vučković, Milica Prostran
We previously showed that magnesium sulfate (MS) has systemic antinociceptive and local peripheral pronociceptive effects. The role of transient receptor potential (TRP) channels and acid-sensing ion channels (ASICs) in the mechanism of action of MS has not been investigated in detail. The aim of this study was to explore the participation of TRP channels in the pronociceptive action of MS in rats after its intraplantar injection. The paw withdrawal threshold (PWT) to mechanical stimuli was measured by the electronic von Frey test...
September 28, 2016: Neuroscience
Hiroshi Mihara, Nobuhiro Suzuki, Jibran Sualeh Muhammad, Sohachi Nanjo, Takayuki Ando, Haruka Fujinami, Shinya Kajiura, Ayumu Hosokawa, Toshiro Sugiyama
BACKGROUND: Helicobacter pylori (HP) infection induces methylation silencing of specific genes in gastric epithelium. Various stimuli activate the nonselective cation channel TRPV4, which is expressed in gastric epithelium where it detects mechanical stimuli and promotes ATP release. As CpG islands in TRPV4 are methylated in HP-infected gastric epithelium, we evaluated HP infection-dependent changes in TRPV4 expression in gastric epithelium. MATERIALS AND METHODS: Human gastric biopsy samples, a human gastric cancer cell line (AGS), and a normal gastric epithelial cell line (GES-1) were used to detect TRPV4 mRNA and protein expression by RT-PCR and Western blotting, respectively...
September 30, 2016: Helicobacter
Yujing Tian, Mengwen Qi, Zhiwen Hong, Yingchun Li, Yibiao Yuan, Yimei Du, Lei Chen, Ling Chen
Neurogenesis plays an important role in adult hippocampal function, and this process can be modulated by intracellular calcium. The activation of transient receptor potential vanilloid 4 (TRPV4) induces an increase in intracellular calcium concentration, but whether neurogenesis can be modulated by TRPV4 activation remains unclear. Here, we report that intracerebroventricular injection of the TRPV4 agonist GSK1016790A for 5 days enhanced the proliferation of stem cells in the hippocampal dentate gyrus (DG) of adult mice without affecting neurite growth, differentiation, or survival of newborn cells...
September 22, 2016: Molecular Neurobiology
Naoki Tsuno, Akira Yukimasa, Osamu Yoshida, Yusuke Ichihashi, Takatsugu Inoue, Tatsuhiko Ueno, Hiroki Yamaguchi, Hidetoshi Matsuda, Satoko Funaki, Natsue Yamanada, Miki Tanimura, Daiki Nagamatsu, Yoko Nishimura, Tetsuji Ito, Masahiko Soga, Narumi Horita, Miyuki Yamamoto, Mikie Hinata, Masayuki Imai, Yasuhide Morioka, Toshiyuki Kanemasa, Gaku Sakaguchi, Yasuyoshi Iso
A novel series of 2',4'-dimethyl-[4,5'-bithiazol]-2-yl amino derivatives were found by high throughput screening of the TRPV4 receptor, at which these compounds showed competitive antagonist potential against 4α-phorbol 12,13-didecanoate (4αPDD) as the selective TRPV4 agonist and showed excellent selectivity for TRPV1, N-type and L-type calcium ion channels, but poor ADME profile. In our SAR strategy, we found that the lead molecule 1 also having the unique 3-oxa-9-azabicyclo [3.3.1] nonan-7-one on the right part showed potent TRPV4 antagonist activity, good solubility at pH 6...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
Estella Zuccolo, Silvia Dragoni, Valentina Poletto, Paolo Catarsi, Daniele Guido, Alessandra Rappa, Marta Reforgiato, Francesco Lodola, Dmitry Lim, Vittorio Rosti, Germano Guerra, Francesco Moccia
Arachidonic acid (AA) stimulates endothelial cell (EC) proliferation through an increase in intracellular Ca(2+) concentration ([Ca(2+)]i), that, in turn, promotes nitric oxide (NO) release. AA-evoked Ca(2+) signals are mainly mediated by Transient Receptor Potential Vanilloid 4 (TRPV4) channels. Circulating endothelial colony forming cells (ECFCs) represent the only established precursors of ECs. In the present study, we therefore, sought to elucidate whether AA promotes human ECFC (hECFC) proliferation through an increase in [Ca(2+)]i and the following activation of the endothelial NO synthase (eNOS)...
September 12, 2016: Vascular Pharmacology
Naoki Tsuno, Akira Yukimasa, Osamu Yoshida, Shinji Suzuki, Hiromi Nakai, Tomoyuki Ogawa, Motohiro Fujiu, Kenji Takaya, Azusa Nozu, Hiroki Yamaguchi, Hidetoshi Matsuda, Satoko Funaki, Yoko Nishimura, Tetsuji Ito, Daiki Nagamatsu, Toshiyuki Asaki, Narumi Horita, Miyuki Yamamoto, Mikie Hinata, Masahiko Soga, Masayuki Imai, Yasuhide Morioka, Toshiyuki Kanemasa, Gaku Sakaguchi, Yasuyoshi Iso
A series of 2',4'-dimethyl-[4,5'-bithiazol]-2-yl amino derivatives have been identified as selective TRPV4 antagonists that display inhibition potencies against 4α-phorbol 12,13-didecanoate (4αPDD), well known as a TRPV4 selective agonist and/or a hypotonicity. In particular, 9-(6-((2',4'-dimethyl-[4,5'-bithiazol]-2-yl)amino)nicotinoyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one showed an analgesic effect in Freund's Complete Adjuvant (FCA) induced mechanical hyperalgesia model in guinea pig (reported in Part 1)...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
Zhiwen Hong, Yujing Tian, Mengwen Qi, Yingchun Li, Yimei Du, Lei Chen, Wentao Liu, Ling Chen
The balance between excitatory and inhibitory neurotransmitter systems is crucial for the modulation of neuronal excitability in the central nervous system (CNS). The activation of transient receptor potential vanilloid 4 (TRPV4) is reported to enhance the response of hippocampal glutamate receptors, but whether the inhibitory neurotransmitter system can be regulated by TRPV4 remains unknown. γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS. Here, we show that application of transient receptor potential vanilloid 4 (TRPV4) synthetic (GSK1016790A or 4α-PDD) or endogenous agonist (5,6-EET) inhibited GABA-activated current (I GABA) in hippocampal CA1 pyramidal neurons, which was blocked by specific antagonists of TRPV4 and of GABAA receptors...
2016: Frontiers in Molecular Neuroscience
D E Naumov, V P Kolosov, J M Perelman, A G Prikhodko
The effect of single nucleotide polymorphisms (SNP) of TRPV4 gene on the development of airway hyperresponsiveness (39.7% of cases) in response to the decrease in osmolarity under inspiration of distilled water aerosol was studies in 189 patients with uncontrolled bronchial asthma. rs6606743 SNP was found to significantly contribute to the development of osmotic airway hyperresponsiveness. Analysis of the dominant genetic model revealed substantial prevalence of AG + GG genotype frequency in the group of patients with asthma with osmotic hyperresponsiveness in comparison with the patients who had negative response to bronchoprovocation...
July 2016: Doklady. Biochemistry and Biophysics
Shifeng Wang, Chenxi Zhai, Yanling Zhang, Yangyang Yu, Yuxin Zhang, Lianghui Ma, Shiyou Li, Yanjiang Qiao
The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be clarified. The current study aimed to find anti-nociceptive candidates targeting transient receptor potential ankyrin 1 (TRPA1), a receptor that implicates in hyperalgesia and neurogenic inflammation. In the current study, 156 chemicals were tested for blocking HEK293/TRPA1 ion channel by calcium-influx assay...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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